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Updated: Jun 21, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors

D Dworakowska1, E Wlodek, C A Leontiou

  • 1Barts and the London School of Medicine, Centre for Endocrinology, London, UK.

Endocrine-Related Cancer
|July 22, 2009
PubMed

Insights

Pituitary adenoma cells show increased activity in the Raf/MEK/ERK pathway, suggesting abnormal cell growth signaling. Downstream effects are attenuated, possibly by cellular senescence in these tumors.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • The Raf/MEK/ERK and PI3K/Akt/mTOR pathways are crucial for cell growth and tumor development.
  • Previous studies indicated B-Raf and Akt overexpression in pituitary adenomas.

Purpose of the Study:

  • To investigate the expression of downstream components and effectors of the Raf/MEK/ERK and PI3K/Akt/mTOR pathways in various pituitary adenoma subtypes.
  • To compare these expressions with normal pituitary tissue.

Main Methods:

  • Western immunoblotting was used to assess protein expression (phosphorylated and total forms).
  • Quantitative RT-PCR was employed to evaluate mRNA expression.
  • Tissue samples included 16 non-functioning pituitary adenomas (NFPAs), 6 GH-omas, 6 prolactinomas, 6 ACTH-omas, and 16 normal pituitaries.

Main Results:

  • Phosphorylated MEK1/2 and ERK1/2 levels were significantly elevated in all pituitary adenoma subtypes compared to controls.
  • No significant differences were observed in phosphorylated/total mTOR, TSC2, or p70S6K expression.
  • c-MYC phosphorylation at Thr58/Ser62 was decreased, while CYCLIN D1 expression was elevated only in NFPAs.
  • mRNA levels for MEK1, MEK2, ERK1, ERK2, c-MYC, and CCND1 were similar across all groups.

Conclusions:

  • Pituitary adenomas exhibit initial upregulation in the Raf/MEK/ERK and PI3K/Akt/mTOR pathways, suggesting aberrant pro-proliferative signaling.
  • Downstream pathway alterations may be attenuated by mechanisms like cellular senescence in these benign tumors.

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